The proposed research will invent, develop, and deploy novel force microscopes, new molecular markers, and new image analysis to support research in cell biology, thrombosis (clotting), and airways (breathing). Researchers are working with nineteen collaborators working on basic research and health issues ranging from surgery planning for pediatric patients with narrowed airways to cystic fibrosis, blood clotting disorders, and skin and other cancers. The novel microscope technologies include a 12-lens high-throughput robotic microscope, microfabricated post arrays to measure elasticity of blood and mucus, and a microscope that can image both vertically and horizontally through cells. The new molecular markers include molecules that glow to indicate when specific cellular activities occur and molecules that change and influence cell behavior in response to specific frequencies of light. The new image analysis includes merging 3D images from high- resolution and fluorescence microscopes to provide a more complete view inside cells, image analysis techniques that can learn how to distinguish cancerous from normal cells on their own, and methods that tie together both image analysis and genetic information to better predict disease. The results will be brought into broad use by reporting them in publications, by presenting them at conferences, by releasing them as open- source software, by incorporating them into commercial products, and by teaching about them at annual workshops.